The properties and activation mechanisms of the angiotensin II (AII) receptor were studied in rat and bovine adrenal glomerulosa cells and in Xenopus laevis oocytes after expression of AII receptors from poly(A)+ mRNA isolated from adrenal glomerulosa cells and other AII target tissues. The inhibitory action of somatostatin on AII-stimulated aldosterone production in rat glomerulosa cells was found to be related to its Gi-mediated inhibition of basal cAMP levels in the glomerulosa cell rather than to any effect on cytoplasmic calcium levels. The stimulatory action of AII on phosphoinositide hydrolysis was associated not only with rapid production and degradation of Ins(1,4,5)P3, but also with short-term and marked long-term changes in several highly phosphorylated inositols. These included early increases in Ins(1,3,4,6)P4 and Ins (3,4,5,6)P4, as well as the Ins(1,3,4,5)P4 derived from Ins(14,5)P3, and progressive increases in Ins(1,3,4,6)P4 and Ins(3,4,5,6)P4, the precursors of InsP5. The cAMP-mediated secretagogue, ACTH, also enhanced AII-stimulated increases in the new InsP4 isomers, by increasing the activity of the 6-kinase enzyme. Thus, the reactions by which Ins(1,3,4,6)P4 and Ins(3,4,5,6)P4 are formed and converted to InsP5 are influenced by agonists acting through both calcium- and cAMP-dependent mechanisms. The conversion of InsP5 to InsP6 was demonstrated in Xenopus oocytes, providing the first evidence for this metabolic step in vertebrate cells. Analysis of the actions of Ins(1,4,5)P3 and Ins(1,3,4,5)P4 on calcium mobilization from adrenal microsomes revealed that the tetrakisphosphate stimulates calcium release from a discrete intracellular store and appears to operate through a receptor site that is distinct from the well characterized receptor for Ins(1,4,5)P3. The other intracellular messenger derived from AII-stimulated phosphoinositide hydrolysis, diacylglycerol (DAG), exhibited a biphasic increase in agonist-stimulated glomerulosa cells, concomitant with the formation of Ins(1,4,5)P3. The initial phases of both InsP3 and DAG responses to AII were not affected by the absence of extracellular calcium, whereas the second phase of the InsP3 response was markedly inhibited and DAG formation was only partially impaired. The retention of a substantial DAG response to AII in the absence of concomitant InsP3 formation indicates that a major proportion of the DAG produced during AII action is derived from sources other than phosphoinositides. Studies on the use of the Xenopus oocyte to express AII receptors from adrenal mRNA and to screen cDNA expression libraries revealed that AII stimulates calcium mobilization in follicular oocytes by acting on receptors present in the adherent follicle cells. The ability of AII to induce a calcium-mobilizing signal that is transferred to the oocyte through gap junctions, and accelerates its rate of maturation, suggests that AII may have a physiological role in the control of oocyte development.